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A Degradable Polyethylenimine Derivative with Low Toxicity for Highly Efficient Gene Delivery
Abstract
Routine clinical implementation of human gene therapy awaits safe and efficient gene delivery methods. Polymeric vectors hold promise due to the availability of diverse chemistries, potentially providing targeting, low immunogenicity, nontoxicity, and robustness, but lack sufficient gene delivery efficiency. We have synthesized a versatile group of degradable polycations, through addition of 800-Da polyethylenimine (PEI) to small diacrylate cross-linkers. The degradable polymers reported here are similar in structure, size (14-30 kDa), and DNA-binding properties to commercially available 25-kDa PEI, but mediate gene expression two- to 16-fold more efficiently and are essentially nontoxic. These easily synthesized polymers are some of the most efficient polymeric vectors reported to date and provide a versatile platform for investigation of the effects of polymer structure and degradation rate on gene delivery efficiency.
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Citations
Cited by
Design and development of polymers for gene delivery
Pack, D. W., Hoffman, A. S., Pun, S., & Stayton, P. S. (2005) · Nature Reviews Drug Discovery · doi:10.1038/nrd1775 · Cited by 2,568
Self-citationNonviral vectors for gene delivery
Mintzer, M. A., & Simanek, E. E. (2009) · Chemical Reviews · doi:10.1021/cr800409e · Cited by 2,366
Block copolymer micelles in nanomedicine applications
Cabral, H., Miyata, K., Osada, K., & Kataoka, K. (2018) · Chemical Reviews · doi:10.1021/acs.chemrev.8b00199 · Cited by 1,309
Nucleic Acid Therapeutics Using Polyplexes: A Journey of 50 Years (and Beyond)
Lächelt, U., & Wagner, E. (2015) · Chemical Reviews · doi:10.1021/cr5006793 · Cited by 600
Ren, X., Feng, Y., Guo, J., Wang, H., Li, Q., Yang, J., Hao, X., Lv, J., Ma, N., & Li, W. (2015) · Chemical Society Reviews · doi:10.1039/c4cs00483c · Cited by 573
Metadata
- Authors
- Forrest, M. L., Koerber, J. T., & Pack, D. W.
- Venue
- Bioconjugate Chemistry
- Publisher
- American Chemical Society (ACS)
- Published
- 2003-08-26
- Volume
- 14
- Issue
- 5
- Pages
- 934-940
- ISSN
- 1043-1802 (ISSN-L)
- 1520-4812
- OpenAlex
- W2094101506
- Cited by
- 387
- References
- 0
- FWCI
- 4.40
- Type
- journal article
- Language
- en
- Open access
- closed
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- Forrest, M. L., Koerber, J. T., & Pack, D. W. (2003). A Degradable Polyethylenimine Derivative with Low Toxicity for Highly Efficient Gene Delivery. Bioconjugate Chemistry. https://doi.org/10.1021/bc034014g
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